It has been recognized that microsphere production technology can produce drugs or pharmaceuticals that can be taken up by cells, e.g., cells in an intestinal or stomach wall or lining, and may cross into the bloodstream. Such uptake or absorption into the cell is determined at least in part by the surface chemistry of the microspheres. Uptake of microspheres containing macromolecules, e.g., encapsulated proteins, has also been demonstrated.
Currently in drug production, top-down processes are typically used to produce drug particles. For example, in such processes, particles may be formed using grinding techniques. Further, for example, it has been described that such particles may be formed by removing solvent from a mixture that includes the active ingredient as it is being sprayed into a stream of air, e.g., hot air drying.
Electrohydrodynamic spraying (or electrospray) has been used to produce nanoparticles from, for example, solutions or colloidal suspensions. The electrospray is capable of producing nanoparticles that are 10-100 times smaller than, for example, conventional pneumatic atomization techniques. This size of particles allows product that includes such particles to have 100-10,000 times larger surface area than those produced from the conventional techniques, for a given quantity of spray solution.
The increased surface area forms the basis of enabling technology for various important applications. For example, new chemicals being synthesized as future drug products are decreasing in aqueous solubility to such an extent as to present major delivery and development challenges. If the drug products employ nanoparticles rather than macroparticles, the increased surface area results in a significantly greater dissolution rate and/or higher solubility rate. This may allow for superior and/or even enabling drug delivery. Nanoparticle medicine may increase the bioavailability and speed up the response time of the delivered drug. Thus, nanoparticle technology has the potential to significantly impact the pharmaceutical industry.
As described in U.S. Pat. No. 6,105,571 to Coffee, entitled “Dispensing Device,” issued 22 Aug. 2000, particles are generated that may comprise biologically active material, for example, particles may contain matter such as peptides or large biomolecules such as insulin and/or other pharmaceutical components for enabling delivery of an active component into the blood stream. As indicated therein, electrohydrodynamic processes are used to produce particles, but primarily are used to produce fibres or fibre fragments.
One limiting factor in employing electrospray or electrohydrodynamic techniques for particle generation is that generally only a single spray-nozzle dispenser is used that can deliver only a small quantity of solution, e.g., a few μl/min. A major challenge and problem is the inability to increase the mass throughput from such an electrospray device that can produce nanoparticles so that electrohydrodynamic techniques can be used to deliver industrial quantities particles for use in various products.
U.S. Pat. No. 6,105,571 cited above, shows use of multiple nozzles to produce fibres or particles as described therein. However, problems associated with multiple nozzle approaches are not addressed, e.g., the space charge effect of particles produced using electrospray techniques, arcing between nozzles, etc.